Meta-analysis of NPC2-mediated cholesterol transport in human cancers as a prognostic biomarker with therapeutic implications

Abstract

NPC2 is a lysosomal cholesterol transporter involved in intracellular lipid trafficking and cholesterol homeostasis, processes that have been increasingly implicated in cancer biology. To quantify the clinical impact of NPC2 expression across human malignancies, we analyzed survival data from 2,097 patients evaluated for NPC2 expression in tumor tissues. We conducted a random-effects meta-analysis of four eligible studies assessing NPC2 expression by mRNA (RNA-seq, qRT-PCR) and protein-based methods (immunohistochemistry, Western blot).The cohort included 756 patients with gastric cancer (36.0%), 374 with hepatocellular carcinoma (17.8%), and 967 with gliomas (46.2%). Pooled analyses demonstrated that elevated NPC2 expression was significantly associated with worse overall survival across cancers (HR 1.29, 95% CI 1.10–1.52, p = 0.001; I2 = 56%). In gastric cancer, this association was stronger and highly consistent (HR 1.37, 95% CI 1.18–1.60, p < 0.001; I2 = 0%). These results suggest that NPC2 overexpression identifies a subset of tumors with increased aggressiveness and adverse clinical outcomes. Collectively, these findings support NPC2 as a candidate adverse prognostic biomarker and highlight lysosomal cholesterol trafficking as a pathway of translational interest in cancer biology. Further mechanistic and clinical studies are warranted to clarify the biological role of NPC2 and its potential therapeutic implications.